Ring finger protein 216 loss-of-function induces white matter hyperintensities by inhibiting oligodendroglia proliferation.

White matter hyperintensities (WMHs) refer to a group of diseases with numerous etiologies while oligodendrocytes remain the centerpiece in the pathogenesis of WMHs. Ring Finger Protein 216 (RNF216) encodes a ubiquitin ligase, and its mutation begets WMHs, ataxia, and cognitive decline in patients. Yet no study has revealed the function of RNF216 in oligodendroglia and WHIs before. In this study, we summarized the phenotypes of RNF216-mutation cases and explored the normal distribution of RNF216 in distinct brain regions and neuronal cells by bioinformatic analysis. Furthermore, MO3.13, a human oligodendrocyte cell line, was applied to study the function alteration after RNF216 knockdown. As a result, WMHs were the most common symptom in RNF216-mutated diseases, and RNF216 was indeed relatively enriched in corpus callosum and oligodendroglia in humans. The downregulation of RNF216 in oligodendroglia remarkably hampered cell proliferation by inhibiting the Akt pathway while having no significant effect on cell injury and oligodendrocyte maturation. Combining clinical, bioinformatical, and experimental evidence, our study implied the pivotal role of RNF216 in WMHs which might serve as a potent target in the therapy of WMHs.

Role of Nitrogenous Functional Group Identity in Accelerating 1,2,3-Trichloropropane Degradation by Pyrogenic Carbonaceous Matter (PCM) and Sulfide Using PCM-like Polymers.

Groundwater contamination by 1,2,3-trichloropropane (TCP) poses a unique challenge due to its human toxicity and recalcitrance to degradation. Previous work suggests that nitrogenous functional groups of pyrogenic carbonaceous matter (PCM), such as biochar, are important in accelerating contaminant dechlorination by sulfide. However, the reaction mechanism is unclear due, in part, to PCM's structural complexity. Herein, PCM-like polymers (PLPs) with controlled placement of nitrogenous functional groups [i.e., quaternary ammonium (QA), pyridine, and pyridinium cations (py+)] were employed as model systems to investigate PCM-enhanced TCP degradation by sulfide. Our results suggest that both PLP-QA and PLP-py+ were highly effective in facilitating TCP dechlorination by sulfide with half-lives of 16.91 ± 1.17 and 0.98 ± 0.15 days, respectively, and the reactivity increased with surface nitrogenous group density. A two-step process was proposed for TCP dechlorination, which is initiated by reductive ß-elimination, followed by nucleophilic substitution by surface-bound sulfur nucleophiles. The TCP degradation kinetics were not significantly affected by cocontaminants (i.e., 1,1,1-trichloroethane or trichloroethylene), but were slowed by natural organic matter. Our results show that PLPs containing certain nitrogen functional groups can facilitate the rapid and complete degradation of TCP by sulfide, suggesting that similarly functionalized PCM might form the basis for a novel process for the remediation of TCP-contaminated groundwater.

Acupoint catgut embedding attenuates oxidative stress and cognitive impairment in chronic cerebral ischemia by inhibiting the Ang II/AT1R/NOX axis.

Chronic cerebral ischemia (CCI) is a common neurological disorder, characterized by progressive cognitive impairment. Acupoint catgut embedding (ACE) represents a modern acupuncture form that has shown neuroprotective effects; nevertheless, its effects on CCI and the mechanisms remain largely unknown. Here, we aimed to explore the therapeutic action of ACE in CCI-induced cognitive impairment and its mechanisms. The cognitive function of CCI rats was determined using Morris water maze test, and histopathological changes in the brain were assessed through hematoxylin-eosin (HE) staining. To further explore the molecular mechanisms, the expression levels of oxidative stress markers and the Ang II/AT1R/NOX axis-associated molecules in the hippocampus were evaluated using enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry. Here, we observed that ACE treatment alleviated cognitive dysfunction and histopathological injury in CCI rats. Intriguingly, candesartan (an AT1R blocker) enhanced the beneficial effects of ACE on ameliorating cognitive impairment in CCI rats. Mechanistically, ACE treatment blocked the Ang II/AT1R/NOX pathway and subsequently suppressed oxidative stress, thus mitigating cognitive impairment in CCI. Our findings first reveal that ACE treatment could suppress cognitive impairment in CCI, which might be partly due to the suppression of Ang II/AT1R/NOX axis.

The adenosine A2A receptor in human sperm: its role in sperm motility and association with in vitro fertilization outcomes.

Background: The involvement of ATP and cAMP in sperm function has been extensively documented, but the understanding of the role of adenosine and adenosine receptors remains incomplete. This study aimed to examine the presence of adenosine A2A receptor (A2AR) and study the functional role of A2AR in human sperm. Methods: The presence and localization of A2AR in human sperm were examined by western blotting and immunofluorescence assays. The functional role of A2AR in sperm was assessed by incubating human sperm with an A2AR agonist (regadenoson) and an A2AR antagonist (SCH58261). The sperm level of A2AR was examined by western blotting in normozoospermic and asthenozoospermic men to evaluate the association of A2AR with sperm motility and in vitro fertilization (IVF) outcomes. Results: A2AR with a molecular weight of 43 kDa was detected in the tail of human sperm. SCH58261 decreased the motility, penetration ability, intracellular Ca2+ concentration, and CatSper current of human sperm. Although regadenoson did not affect these sperm parameters, it alleviated the adverse effects of SCH58261 on these parameters. In addition, the mean level of A2AR in sperm from asthenozoospermic men was lower than that in sperm from normozoospermic men. The sperm level of A2AR was positively correlated with progressive motility. Furthermore, the fertilization rate during IVF was lower in men with decreased sperm level of A2AR than in men with normal sperm level of A2AR. Conclusions: These results indicate that A2AR is important for human sperm motility and is associated with IVF outcome.

Chest non­contrasted computed tomography in detecting acute pulmonary thromboembolism: A single­center retrospective study.

The object of the study was to evaluate comprehensively the value of chest non-contrasted CT (NC-CT) in detecting acute pulmonary thromboembolism (APE). All patients were categorized into two groups: i) With APE; and ii) without APE based on clinical diagnosis. Using the clot distribution on computed tomography pulmonary angiography (CTPA), APE was divided into central and peripheral APE. Imaging features including hyperdense lumen sign and peripheral wedge-shaped opacity on chest NC-CT were evaluated. The attenuation value of peripheral wedge-shaped opacity on NC-CT was compared between patients with and without APE. Among the 273 patients, there were 110 patients with APE, 49 patients with central APE and 61 patients with peripheral APE and 163 patients without APE. The hyperdense lumen sign had a sensitivity of 30.0% and a specificity of 97.6% in detecting APE. The sensitivity and specificity of hyperdense lumen sign in detecting central APE were 57.1 and 97.6%, respectively, while the relevant percentages in detecting peripheral APE were 8.2 and 97.6%, respectively. The mean attenuation value of peripheral wedge-shaped opacity in patients with APE was significantly lower than that in patients without APE (P<0.001). Regarding the age-adjusted D-dimer, there was a decrease of eight D-dimer positive cases for patients >50 years old without APE, confirmed by CTPA. In conclusion, chest NC-CT cannot be used as an alternative modality for CTPA in diagnosing APE, however, the hyperdense lumen sign had high specificity in the diagnosis of central APE. Patients with this symptom and increased D-dimer may not require further CTPA. The lower attenuation value of peripheral wedge-shaped opacity on NC-CT suggested APE, and CTPA confirmation was required. The age-adjusted D-dimer had higher specificity in excluding APE.

Unraveling the Synergistic Mechanism of Ir Species with Various Electron Densities over an Ir/ZSM-5 Catalyst Enables High-Efficiency NO Reduction by CO.

Selective catalytic reduction using CO as a reducing agent (CO-SCR) has exhibited its application potential in coal-fired, steel, and other industrial sectors. In comparison to NH3-SCR, CO-SCR can achieve synergistic control of CO and NO pollutants, making it a powerful denitrification technology that treats waste with waste. Unfortunately, the competitive adsorption of O2 and NO on CO-SCR catalysts inhibits efficient conversion of NOx under O2-containing conditions. In this work, we obtained two Ir sites with different electron densities, Ir1 single atoms in the oxidized Irδ+ state and Ir0 nanoparticles in the metallic state, by controlled pretreatment of the Ir/ZSM-5 catalyst with H2 at 200 °C. The coexistence of Ir1 single atoms and Ir0 nanoparticles on ZSM-5 creates a synergistic effect, which facilitates the reduction of NO through CO in the presence of O2, following the Langmuir-Hinshelwood mechanism. The ONNO dimer is formed on the Ir1 single atom sites and then spills over to the neighboring Ir0 nanoparticles for subsequent reduction to N2 by CO. Specifically, this tandem reaction enables 83% NO conversion and 100% CO conversion on an Ir-based catalyst at 250 °C under 3% O2.

Experimental and Computational Study of Pyrogenic Carbonaceous Matter Facilitated Hydrolysis of 2,4-Dinitroanisole (DNAN).

This study investigated the reaction pathway of 2,4-dinitroanisole (DNAN) on the pyrogenic carbonaceous matter (PCM) to assess the scope and mechanism of PCM-facilitated surface hydrolysis. DNAN degradation was observed at pH 11.5 and 25 °C with a model PCM, graphite, whereas no significant decay occurred without graphite. Experiments were performed at pH 11.5 due to the lack of DNAN decay at pH below 11.0, which was consistent with previous studies. Graphite exhibited a 1.78-fold enhancement toward DNAN decay at 65 °C and pH 11.5 relative to homogeneous solution by lowering the activation energy for DNAN hydrolysis by 54.3 ± 3.9%. This is supported by our results from the computational modeling using Car-Parrinello simulations by ab initio molecular dynamics/molecular mechanics (AIMD/MM) and DFT free energy simulations, which suggest that PCM effectively lowered the reaction barriers by approximately 8 kcal mol-1 compared to a homogeneous solution. Quaternary ammonium (QA)-modified activated carbon performed the best among several PCMs by reducing DNAN half-life from 185 to 2.5 days at pH 11.5 and 25 °C while maintaining its reactivity over 10 consecutive additions of DNAN. We propose that PCM can affect the thermodynamics and kinetics of hydrolysis reactions by confining the reaction species near PCM surfaces, thus making them less accessible to solvent molecules and creating an environment with a weaker dielectric constant that favors nucleophilic substitution reactions. Nitrite formation during DNAN decay confirmed a denitration pathway, whereas demethylation, the preferred pathway in homogeneous solution, produces 2,4-dinitrophenol (DNP). Denitration catalyzed by PCM is advantageous to demethylation because nitrite is less toxic than DNAN and DNP. These findings provide critical insights for reactive adsorbent design that has broad implications for catalyst design and pollutant abatement.

MircoRNA-25-3p in skin precursor cell-induced Schwann cell-derived extracellular vesicles promotes axon regeneration by targeting Tgif1.

Nerve injury often leads to severe dysfunction because of the lack of axon regeneration in adult mammal. Intriguingly a series of extracellular vesicles (EVs) have the obvious ability to accelerate the nerve repair. However, the detailed molecular mechanisms to describe that EVs switch neuron from a transmitter to a regenerative state have not been elucidated. This study elucidated the microRNA (miRNA) expression profiles of two types of EVs that promote nerve regeneration. The functions of these miRNAs were screened in vitro. Among the 12 overlapping miRNAs, miR-25-3p was selected for further analysis as it markedly promoted axon regeneration both in vivo and in vitro. Furthermore, knockdown experiments confirmed that PTEN and Klf4, which are the major inhibitors of axon regeneration, were the direct targets of miR-25-3p in dorsal root ganglion (DRG) neurons. The utilization of luciferase reporter assays and functional tests provided evidence that miR-25-3p enhances axon regeneration by targeting Tgif1. Additionally, miR-25-3p upregulated the phosphorylation of Erk. Furthermore, Rapamycin modulated the expression of miR-25-3p in DRG neurons. Finally, the pro-axon regeneration effects of EVs were confirmed by overexpressing miR-25-3p and Tgif1 knockdown in the optic nerve crush model. Thus, the enrichment of miR-25-3p in EVs suggests that it regulates axon regeneration, proving a potential cell-free treatment strategy for nerve injury.

Nucleic-acid-base photofunctional cocrystal for information security and antimicrobial applications.

Cocrystal engineering is an efficient and simple strategy to construct functional materials, especially for the exploitation of novel and multifunctional materials. Herein, we report two kinds of nucleic-acid-base cocrystal systems that imitate the strong hydrogen bond interactions constructed in the form of complementary base pairing. The two cocrystals studied exhibit different colors of phosphorescence from their monomeric counterparts and show the feature of rare high-temperature phosphorescence. Mechanistic studies reveal that the strong hydrogen bond network stabilizes the triplet state and suppresses non-radiative transitions, resulting in phosphorescence even at 425 K. Moreover, the isolation effects of the hydrogen bond network regulate the interactions between the phosphor groups, realizing the manipulation from aggregation to single-molecule phosphorescence. Benefiting from the long-lived triplet state with a high quantum yield, the generation of reactive oxygen species by energy transfer is also available to utilize for some applications such as in photodynamic therapy and broad-spectrum microbicidal effects. In vitro experiments show that the cocrystals efficiently kill bacteria on a tooth surface and significantly help prevent dental caries. This work not only provides deep insight into the relationship of the structure-properties of cocrystal systems, but also facilitates the design of multifunctional cocrystal materials and enriches their potential applications.

The cyclimids: Degron-inspired cereblon binders for targeted protein degradation.

Cereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer a facile approach for developing potent and selective bifunctional degraders. Quantitative TR-FRET-based characterization of 60 cyclimid degraders in binary and ternary complexes across different substrates revealed that ternary complex binding affinities correlated strongly with cellular degradation efficiency. Our studies establish the unique properties of the cyclimids as versatile warheads in TPD and a systematic biochemical approach for quantifying ternary complex formation to predict their cellular degradation activity, which together will accelerate the development of ligands that engage CRBN.

DTTZ suppresses ferroptosis and reverses mitochondrial dysfunction in normal tissues affected by chemotherapy.

Conventional antineoplastic therapies cause severe normal tissue damage and existing cytoprotectants with acute toxicities or potential tumor protection limit their clinical application. We evaluated the selective cytoprotection of 2,2-dimethylthiazolidine hydrochloride in this study, which could protect normal tissue toxicity without interfering antineoplastic therapies. By using diverse cell lines and A549 xenograft model, we discovered a synthetic aminothiol 2,2-dimethylthiazolidine hydrochloride selectively diminished normal cellular ferroptosis via SystemXc-/Glutathione Peroxidase 4 pathway upon antineoplastic therapies without interfering the anticancer efficacy. We revealed the malignant and non-malignant tissues presenting different energy metabolism patterns. And cisplatin induces disparate replicative stress, contributing to the distinguishable cytoprotection of 2,2-dimethylthiazolidine in normal and tumor cells. The compound pre-application could mitigate cisplatin-induced normal cellular mitochondrial oxidative phosphorylation (OXPHOS) dysfunction. Pharmacologic ablation of mitochondria reversed 2,2-dimethylthiazolidine chemoprotection against cisplatin in the normal cell line. Combined, these results provide a potential therapeutic adjuvant to selectively diminish normal tissue damages retaining antineoplastic efficacy.

Establishment of FDHSi003-A, a human induced pluripotent stem cell (hiPSC) line with a mutation of RNF216 c.1948G > T.

Gordon Holmes Syndrome (GDHS) is a hereditary neurodegenerative disease mainly associated with mutations of RNF216. We established a human induced pluripotent stem cell (hiPSC) line, FDHSi003-A, derived from PBMC of a patient baring a mutation of RNF216 c.1948G > T, who shows typical symptoms of GDHS. The generated FDHSi003-A expresses pluripotency markers, displays a normal karyotype, and has the potency to differentiate into all three germ layers. Thus, FDHSi003-A is an ideal model to investigate the mechanism of RNF216 in GDHS.

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/SHOC2 feedback loop.

OBJECTIVE: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. METHODS: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. RESULTS: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. CONCLUSION: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

Clot ratio, new clot burden score with deep learning, correlates with the risk stratification of patients with acute pulmonary embolism.

Background: Risk stratification for patients with acute pulmonary embolism (APE) is significantly important for treatment and prognosis evaluation. We aimed to develop a novel clot burden score on computed tomography pulmonary angiography (CTPA) based on deep learning (DL) algorithm for risk stratification of APE. Methods: The study retrospectively enrolled patients newly diagnosed with APE in China-Japan Friendship Hospital consecutively. We collected baseline data and CTPA parameters, and calculated four different clot burden scores, including Qanadli score, Mastora score, clot volume and clot ratio. The former two were calculated by two radiologists separately, while clot volume and clot ratio were based on the DL algorithm. The area under the curve (AUC) of four clot burden scores were analyzed. Results: Seventy patients were enrolled, including 17 in high-/intermediate-high risk and 53 in low-/intermediate-low risk. Clot burden was related to the risk stratification of APE. Among four clot burden scores, clot ratio had the highest AUC (0.719, 95% CI: 0.569-0.868) to predict patients with higher risk. In the patients with hemodynamically stable APE, only clot ratio presented statistical difference (P=0.046). Conclusions: Clot ratio is a new imaging marker of clot burden which correlates with the risk stratification of patients with APE. Higher clot ratio may indicate higher risk and acute right ventricular dysfunction in patients with hemodynamically stable status.

Role of automated functional imaging and myocardial work in assessment of cardiac function in children with obstructive sleep apnea.

BACKGROUND: Early identification of abnormal left ventricular function in children with obstructive sleep apnea (OSA) is difficult using conventional echocardiographic indices and commonly used clinical markers of myocardial damage. We sought to investigate the value of automatic function imaging and myocardial work parameters in predicting early cardiac impairment in children having OSA with preserved left heart function and thereby identifying an optimal index for assessment. PATIENTS AND METHODS: Fifty-two children who presented with symptoms of nocturnal sleep snoring and open-mouth breathing and 34 healthy controls were enrolled in this study. Clinical characteristics and conventional echocardiographic data were collected, and image analysis was performed using two-dimensional speckle-tracking echocardiography to obtain left ventricular global longitudinal strain (GLS), post-systolic index, peak strain dispersion, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. RESULTS: Children with OSA had significantly lower GLS, GWI, and GCW than those without (P < 0.05). Additionally, GWI (ß = -32.87, 95% CI: -53.47 to -12.27), and GCW (ß = -35.09, 95% CI: -55.35 to -14.84) were found to correlate with the disease severity in the multiple linear regression mode, with worsening values observed as the severity of the disease increased. ROC curve analysis revealed that GCW was the best predictor of myocardial dysfunction, with an AUC of 0.809 (P < 0.001), and the best cutoff point for diagnosing myocardial damage in children with OSA was 1965.5 mmHg%, with a sensitivity of 92.5% and a specificity of 58.7%. CONCLUSIONS: GLS, GWI, and GCW were identified as predictors of myocardial dysfunction in children with OSA, with GCW being the best predictor.

Single-Atom Ru Alloyed with Ni Nanoparticles Boosts CO2 Methanation.

Designing catalysts to proceed with catalytic reactions along the desired reaction pathways, e.g., CO2 methanation, has received much attention but remains a huge challenge. This work reports one Ru1Ni single-atom alloy (SAA) catalyst (Ru1Ni/SiO2) prepared via a galvanic replacement reaction between RuCl3 and Ni nanoparticles (NPs) derived from the reduction of Ni phyllosilicate (Ni-ph). Ru1Ni/SiO2 achieved much improved selectivity toward hydrogenation of CO2 to CH4 and catalytic activity (Turnover frequency (TOF) value: 40.00 × 10-3 s-1), much higher than those of Ni/SiO2 (TOF value: 4.40 × 10-3 s-1) and most reported Ni-based catalysts (TOF value: 1.03 × 10-3-11.00 × 10-3 s-1). Experimental studies verify that Ru single atoms are anchored onto the Ni NPs surface via the Ru1-Ni coordination accompanied by electron transfer from Ru1 to Ni. Both in situ experiments and theoretical calculations confirm that the interface sites of Ru1Ni-SAA are the intrinsic active sites, which promote the direct dissociation of CO2 and lower the energy barrier for the hydrogenation of CO* intermediate, thereby directing and enhancing the CO2 hydrogenation to CH4.

A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score, revised Geneva score, and Years algorithm.

BACKGROUND: Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models. METHODS: This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Naïve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis. RESULTS: The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. CONCLUSIONS: Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/ SHOC2 feedback loop

ABSTRACT Objective: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. Methods: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. Results: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. Conclusion: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

Catalytic removal of gaseous pollutant NO using CO: Catalyst structure and reaction mechanism.

Carbon monoxide (CO) has recently been considered an ideal reducing agent to replace NH3 in selective catalytic reduction of NOx (NH3-SCR). This shift is particularly relevant in diesel engines, coal-fired industry, the iron and steel industry, of which generate substantial amounts of CO due to incomplete combustion. Developing high-performance catalysts remain a critical challenge for commercializing this technology. The active sites on catalyst surface play a crucial role in the various microscopic reaction steps of this reaction. This work provides a comprehensive overview and insights into the reaction mechanism of active sites on transition metal- and noble metal-based catalysts, including the types of intermediates and active sites, as well as the conversion mechanism of active molecules or atoms. In addition, the effects of factors such as O2, SO2, and alkali metals, on NO reduction by CO were discussed, and the prospects for catalyst design are proposed. It is hoped to provide theoretical guidance for the rational design of efficient CO selective catalytic denitration materials based on the structure-activity relations.

Comparison of cardiovascular metrics on computed tomography pulmonary angiography of the updated and old diagnostic criteria for pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension.

Background: In the 2022 European Society of Cardiology (ESC) and the European Respiratory Society (ERS) guidelines, the diagnostic criteria for pulmonary hypertension (PH) included a reduced mean pulmonary artery pressure (mPAP) of 20 mmHg (mPAP >20 mmHg). This study aimed to reassess cardiovascular metrics on computed tomography pulmonary angiography (CTPA) for chronic thromboembolic pulmonary hypertension (CTEPH) to optimize the timely diagnosis of patients with suspected PH. Methods: Patients with suspected CTEPH who underwent CTPA and right heart catheterization (RHC) between January 2019 and December 2022 in China-Japan Friendship Hospital were retrospectively included. They were grouped into CTEPH and non-PH groups according to the new and old criteria (2022 and 2015 ESC/ERS guidelines) for the diagnosis of PH. Cardiovascular metrics including the main pulmonary artery diameter (MPAd), Cobb angle, and right ventricular free wall thickness (RVWT), among others, were measured. The correlation of these metrics with hemodynamic data was analyzed with Spearman rank correlation analysis, while the differences in cardiovascular metrics between the updated (mPAP >20 mmHg) and old PH criteria (mPAP ≥25 mmHg) were compared with independent samples t-test or the Mann-Whitney test. Receiver operator characteristic (ROC) curve analysis was performed for the prediction model. Results: The study enrolled 180 patients (males n=86; age 55.5±12.0 years old). According to the old guidelines, 119 patients were placed into the PH group (mPAP ≥25 mmHg) , while according to the new guidelines, 130 patients were placed into the PH group (mPAP >20 mmHg). Cardiovascular metrics on CTPA between the updated and old guidelines were comparable (P>0.05). Compared to other metrics, an MPAd of 30.4 mm exhibited the highest area under the curve (AUC: 0.934±0.021), with a sensitivity of 0.88 and specificity of 0.90. MPAd [odds ratio (OR) =1.271], transverse diameter of the right ventricle (RVtd; OR =1.176), Cobb angle (OR =1.108), and RVWT (OR =3.655) were independent factors for diagnosing CTEPH (P<0.05). Cobb angle, right and left ventricular transverse diameter ratio, and right and left ventricular area ratio moderately correlated with mPAP (r=0.586, r=0.583, r=0.629) and pulmonary vascular resistance (PVR) (r=0.613, r=0.593, r=0.642). Conclusions: Cardiovascular metrics on CTPA were comparable between the new and old guidelines for CTEPH diagnosis. Cardiovascular metrics on CTPA can noninvasively assess the hemodynamics of patients with CTEPH.